7.1 CLEFT LIP AND PALATE

EPIDEMIOLOGY/GENETICS

Definition A facial cleft involving the upper lip or palate, usually occurring to the left or right of midline, the cleft lip or cleft palate may occur as an isolated malformation or as part of a multiple-malformation syndrome. Midline facial clefts may be associated with underlying brain malformations, especially holoprosencephaly.

Epidemiology Occurrence is 1 in 1000 births (M2:F1) for cleft lip or cleft palate and 0.65 in 1000 births for isolated cleft palate (M2:F3). There is marked ethnic and racial variation in incidence (Caucasian 1 to African American 0.6). Some studies suggested that maternal preconceptional folic acid supplementation decreases the incidence of nonsyndromic clefts. Medial facial clefts account for less than 1% of all facial clefts.

Embryology The primary palate (anterior to incisive foramina) and secondary palate (posterior to the incisive foramina) are embryologically distinct. The upper lip and primary palate have usually fused by the seventh week of gestation. Formation of the secondary palate occurs by fusion of the palatal shelf by the 12th week. Cleft lip and cleft palate are due to a failure of union of the frontonasal process of the face with the lateral maxillary prominences at about 7 weeks’ gestation. Approximately 60% of cases are isolated. Almost 300 multiple-malformation syndromes have been described with cleft lip or cleft palate. Chromosomal abnormalities may be found in 3.9% of isolated cleft lip and palate and in up to 63% when associated anomalies are present. A variety of chromosomal abnormalities have been implicated, including the 22q11 deletion. The most common associated anomalies are those involving the lumbar and cervical spine (33%) and heart (24%).

Midline facial clefts are the result of a deficient frontonasal development process that is normally induced by the underlying brain. Midline facial clefts with underlying brain abnormalities are seen in trisomy 13, as well as other chromosomal abnormalities and genetic syndromes.

Inheritance Patterns Most isolated cleft lips or cleft palates show multifactorial inheritance, but up to 20% are a component of dominant, recessive, and X-linked syndromes (including van der Woude syndrome). Determining the pattern of inheritance depends on an accurate diagnosis.

Prognosis The prognosis for a good cosmetic and functional repair with isolated cleft lip or cleft palate is excellent. Otherwise, the prognosis is dependent on any associated malformations or a syndrome diagnosis. Midline clefts, if they are associated with underlying brain malformations, usually carry a poor prognosis.